根据PD-L1表达和免疫浸润对肿瘤免疫微环境（TIME）进行分类可预测晚期NSCLC患者对免疫治疗加化疗的反应

SCI

6 April 2023

Classification of Tumor Immune Microenvironment (TIME) According to PD-L1 Expression and Immune Infiltration Predicts Response to Immunotherapy plus Chemotherapy in Advanced NSCLC Patients 

(J Thorac Oncol IF: 15.61;)

Background 研究背景   

According to mechanisms of adaptive immune resistance, tumor immune microenvironment  (TIME) is classified into four types: PD-L1−/TIL− (type I); PD-L1+/TIL+ (type II); PD-L1−/TIL+  (type III); and PD-L1+/TIL− (type IV). However, the relationship of TIME classification model and immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced non-small cell lung cancer (NSCLC). 

根据适应性免疫抵抗的机制，肿瘤免疫微环境（TIME）被分为四种类型：PD-L1/TIL-（I型）；PD-L1+/TIL+（II型）；PD-L1/TIL+（III型）；以及PD-L1+/TIL-（IV型）。然而，在晚期非小细胞肺癌（NSCLC）患者中，TIME分类模型与免疫疗法疗效的关系还没有被任何大规模的随机对照临床试验所验证。

Methods 研究方法   

Based on RNA-sequencing and immunohistochemistry data from ORIENT-11 study, we optimized TIME classification model and evaluated its predictive value for efficacy of immunotherapy plus chemotherapy. 

基于ORIENT-11研究的RNA测序和免疫组化数据，我们优化了TIME分类模型，并评估了其对免疫治疗加化疗疗效的预测价值。

Results 结果  

PD-L1 mRNA expression and immune score calculated by the ESTIMATE method were strongest predictors for efficacy of immunotherapy plus chemotherapy. Therefore, they were determined as optimized definition of TIME classification system. When compared between combination therapy and chemotherapy alone, only type II subpopulation with high immune score and high PD-L1 mRNA expression was significantly associated with improved PFS (HR, 0.12; 95% CI, 0.06-0.25; P<.001) and OS (HR, 0.27; 95% CI, 0.13-0.55; P<.001). In combination group, type II subpopulation had much longer survival time, not even reaching median PFS or OS, but the other three subpopulations were prone to have similar PFS. In chemotherapy group, there was no significant association between survival outcomes and TIME subtypes. 

PD-L1 mRNA表达和用ESTIMATE方法计算的免疫评分是预测免疫治疗加化疗疗效的最强因素。因此，它们被确定为TIME分类系统的优化定义。比较联合治疗和单纯化疗，只有免疫评分高和PD-L1 mRNA表达高的II型亚群与PFS（HR，0.12；95%CI，0.06-0.25；P<.001）和OS（HR，0.27；95%CI，0.13-0.55；P<.001）的改善显著相关。在联合治疗组中，II型亚群的生存时间更长，甚至达不到中位数的PFS或OS，但其他三个亚群容易有类似的PFS。在化疗组，生存结果与TIME亚型之间没有明显的关联。

Conclusion 结论  

Only patients with both high PD-L1 expression and high immune infiltration could benefit from chemotherapy plus immunotherapy in first-line treatment of advanced NSCLC. For patients lacking either PD-L1 expression or immune infiltration, chemotherapy alone might be a better treatment option to avoid unnecessary toxicities and financial burdens. 

在晚期NSCLC的一线治疗中，只有PD-L1高表达和高免疫浸润的患者才能从化疗加免疫治疗中获益。对于缺乏PD-L1表达或免疫浸润的患者，单纯化疗可能是更好的治疗选择，以避免不必要的毒副作用和经济负担。

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